Frailty as a predictor of postoperative outcomes in neurosurgery: a systematic review.

INTRODUCTION: Baseline frailty status has been utilized to predict a wide range of outcomes and guide preoperative decision making in neurosurgery. This systematic review aims to analyze existing literature on the utilization of frailty as a predictor of neurosurgical outcomes. EVIDENCE ACQUISITION: We conducted a systematic review following PRISMA guidelines. Studies that utilized baseline frailty status to predict outcomes after a neurosurgical intervention were included in this systematic review. Studies that utilized sarcopenia as the sole measure of frailty were excluded. PubMed, EMBASE, and Cochrane library was searched from inception to March 1st, 2023, to identify relevant articles. EVIDENCE SYNTHESIS: Overall, 244 studies met the inclusion criteria. The 11-factor modified frailty index (mFI-11) was the most utilized frailty measure (N.=91, 37.2%) followed by the five-factor modified Frailty Index (mFI-5) (N.=80, 32.7%). Spine surgery was the most common subspecialty (N.=131, 53.7%), followed by intracranial tumor resection (N.=57, 23.3%), and post-operative complications were the most reported outcome (N.=130, 53.2%) in neurosurgical frailty studies. The USA and the Bowers author group published the greatest number of articles within the study period (N.=176, 72.1% and N.=37, 15.2%, respectively). CONCLUSIONS: Frailty literature has grown exponentially over the years and has been incorporated into neurosurgical decision making. Although a wide range of frailty indices exist, their utility may vary according to their ability to be incorporated in the outpatient clinical setting.

Continuous Tissue Plasminogen Activator Infusion Using a Minimally Invasive Irrigating Catheter for the Treatment of Intraparenchymal Hemorrhage Within the Basal Ganglia: Case Reports.

BACKGROUND AND IMPORTANCE: Intraparenchymal hemorrhage (IPH) is a debilitating and highly morbid type of stroke with limited effective treatment modalities. Minimally invasive evacuation with tissue plasminogen activator (rt-PA) has demonstrated promise for mortality/functional improvements with adequate clot volume reduction. In this study, we report 2 cases of continuous rt-PA infusion using a closed circuit, dual lumen catheter, and irrigation system (IRRAflow) for IPH treatment. CLINICAL PRESENTATION: A 55-year-old man was admitted for acute onset left hemiparesis; he was found to have right basal ganglia IPH. He was treated with continuous rt-PA irrigation using the IRRAflow device, at a rate of 30 mL/h for 119 hours, with a total volume reduction of 87.8 mL and post-treatment volume of 1.2 mL. At 3-month follow-up, he exhibited a modified Rankin score of 4 and improved hemiparesis. A 39-year-old woman was admitted for acute onset left facial droop, left hemianopsia, and left hemiparesis; she was diagnosed with a right basal ganglia IPH. She was treated with drainage and continuous rt-PA irrigation at 30 mL/h for 24 hours, with a total hematoma volume reduction of 41 mL and with a final post-treatment volume of 9.1 mL. At 3-month follow-up, she exhibited a modified Rankin score of 3 with some improvement in left hemiparesis. CONCLUSION: Continuous rt-PA infusion using a minimally invasive catheter with saline irrigation was feasible and resulted in successful volume reduction in 2 patients with IPH. This technique is similar to the Minimally Invasive Surgery Plus rt-PA for Intracerebral Hemorrhage Evacuation (MISTIE) approach but offers the potential advantages of less breaks in the sterile circuit, continuous intracranial pressure monitoring, and may provide more efficient clot lysis compared with intermittent bolusing.

Baseline Characteristics of Patients With Cavernous Angiomas With Symptomatic Hemorrhage in Multisite Trial Readiness Project.

BACKGROUND AND PURPOSE: Brain cavernous angiomas with symptomatic hemorrhage (CASH) have a high risk of neurological disability from recurrent bleeding. Systematic assessment of baseline features and multisite validation of novel magnetic resonance imaging biomarkers are needed to optimize clinical trial design aimed at novel pharmacotherapies in CASH. METHODS: This prospective, multicenter, observational cohort study included adults with unresected, adjudicated brain CASH within the prior year. Six US sites screened and enrolled patients starting August 2018. Baseline demographics, clinical and imaging features, functional status (modified Rankin Scale and National Institutes of Health Stroke Scale), and patient quality of life outcomes (Patient-Reported Outcomes Measurement Information System-29 and EuroQol-5D) were summarized using descriptive statistics. Patient-Reported Outcomes Measurement Information System-29 scores were standardized against a reference population (mean 50, SD 10), and one-sample t test was performed for each domain. A subgroup underwent harmonized magnetic resonance imaging assessment of lesional iron content with quantitative susceptibility mapping and vascular permeability with dynamic contrast-enhanced quantitative perfusion. RESULTS: As of May 2020, 849 patients were screened and 110 CASH cases enrolled (13% prevalence of trial eligible cases). The average age at consent was 46±16 years, 53% were female, 41% were familial, and 43% were brainstem lesions. At enrollment, ≥90% of the cohort had independent functional outcome (modified Rankin Scale score ≤2 and National Institutes of Health Stroke Scale score <5). However, perceived health problems affecting quality of life were reported in >30% of patients (EuroQol-5D). Patients had significantly worse Patient-Reported Outcomes Measurement Information System-29 scores for anxiety (P=0.007), but better depression (P=0.002) and social satisfaction scores (P=0.012) compared with the general reference population. Mean baseline quantitative susceptibility mapping and permeability of CASH lesion were 0.45±0.17 ppm and 0.39±0.31 mL/100 g per minute, respectively, which were similar to historical CASH cases and consistent across sites. CONCLUSIONS: These baseline features will aid investigators in patient stratification and determining the most appropriate outcome measures for clinical trials of emerging pharmacotherapies in CASH.

Cerebrovascular and cardiovascular disease burden in patients with hereditary hemorrhagic telangiectasia.

INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease with prevalence of approximately 1 in 5000-10,000. We evaluated the prevalence and association of cerebrovascular and cardiovascular comorbidities in HHT patients using national database. METHODS: Retrospective observational study was performed using National Inpatient Sampling (NIS) database for the year 2014. HHT patients and comorbidities were identified using ICD-9 codes. Univariate and multivariate analyses were performed using SAS. RESULTS: Prevalence of HHT was 0.0119% with predominance in White population. Mean age of HHT patients was 59 years. Increased proportion of HHT patients had hypertension (46.8% vs 42%), anemia (28.9% vs 15.1%), chronic pulmonary disease (24.8% vs 16.4%), congestive heart failure (15.7% vs 7.5%), liver disease (7.9% vs 2.8%), migraine (4.5% vs 1.5%), and cerebrovascular malformations (0.8% vs 0.03%), whereas chronic kidney disease (12.7% vs 12.2%), headaches (1.3% vs 1.1%), seizures (0.7% vs 0.9%), transient ischemic attacks (1.06% vs 1.03%), ischemic (1.2% vs 1.0%), and hemorrhagic (0.5% vs 0.3%) strokes were similar to those without HHT. Multivariable model shows increase in cerebrovascular malformations (OR 11.04, CI 2.49-22.26, p < 0.0001), migraine (OR 3.23, CI 2.30-4.52, p < 0.0001), chronic blood loss anemia (OR 6.83, CI 5.36-8.71, p < 0.0001), congestive heart failure (OR 1.55, CI 1.26-1.91, p < 0.0001), chronic pulmonary disease (OR 1.30, CI 1.09-1.56, p = 0.0038), and hepatic disease (OR 2.63, CI 2.01-3.45, p < 0.0001) in HHT patients as compared to non-HHT patients. CONCLUSION: There is a need for a large prospective registry of HHT patients that can corroborate these associations and burden of cerebrovascular and cardiovascular diseases.

Cognitive Impairment After Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

OBJECTIVE: The present systematic review and meta-analysis analyzes the available clinical literature on post-intracerebral hemorrhage (ICH) cognitive impairment. METHODS: We conducted a systematic review with meta-analysis following PRISMA guidelines. A search of bibliographic databases up to July 31, 2020 yielded 2155 studies. Twenty articles were included in our final qualitative systematic review and 18 articles in quantitative meta-analysis. RESULTS: Based on analysis of data from 18 studies (3270 patients), we found prevalence of post-ICH cognitive impairment to be 46% (confidence interval, 35.9-55.9), with a follow-up duration ranging from 8 days to 4 years. The estimated pooled prevalence of cognitive decline decreased over longitudinal follow-up, from 55% (range, 37.7%-71.15%) within 6 months of ICH to 35% (range, 27%-42.7%) with >6 months to 4 years follow-up after ICH. The modalities used to evaluate cognitive performance after ICH in studies varied widely, ranging from global cognitive measures to domain-specific testing. The cognitive domain most commonly affected included nonverbal IQ, information processing speed, executive function, memory, language, and visuoconstructive abilities. Prognostic factors for poor cognitive performance included severity of cortical atrophy, age, lobar ICH location, and higher number of hemorrhages at baseline. CONCLUSIONS: The prevalence of post-ICH cognitive impairment is high. Despite the heterogeneity among studies, the present study identified cognitive domains most commonly affected and predictors of cognitive impairment after ICH. In future, prospective cohort studies with larger sample sizes and standardized cognitive domains testing could more accurately determine prevalence and prognostic factors of post-ICH cognitive decline.

Decision-making for decompressive craniectomy in traumatic brain injury aided by multimodality monitoring: illustrative case.

BACKGROUND: Severe traumatic brain injury (TBI) requires individualized, physiology-based management to avoid secondary brain injury. Recent improvements in quantitative assessments of metabolism, oxygenation, and subtle examination changes may potentially allow for more targeted, rational approaches beyond simple intracranial pressure (ICP)-based management. The authors present a case in which multimodality monitoring assisted in decision-making for decompressive craniectomy. OBSERVATIONS: This patient sustained a severe TBI without mass lesion and was monitored with a multimodality approach. Although imaging did not seem grossly worrisome, ICP, pressure reactivity, brain tissue oxygenation, and pupillary response all began worsening, pushing toward decompressive craniectomy. All parameters normalized after decompression, and the patient had a satisfactory clinical outcome. LESSONS: Given recent conflicting randomized trials on the utility of decompressive craniectomy in severe TBI, precision, physiology-based approaches may offer an improved strategy to determine who is most likely to benefit from aggressive treatment. Trials are underway to test components of these strategies.

Cytokine Registry In Stroke Patients (CRISP): Protocol of a prospective observational study.

Inflammation is an important pathophysiological process after an acute stroke (AS). Pro- and anti-inflammatory molecules (cytokines and interleukins) are the key players during this mechanism. Emerging evidence indicate that these molecules can serve as biomarkers of stroke progression and outcome and as novel therapeutics agents. The aim of this study is to explore the temporal changes in these molecules and validate them as biomarker of AS progression and neurological outcome.The "Cytokine Registry In Stroke Patients (CRISP)" is a prospective cohort study of 600 AS patients presenting to the tertiary hospital with-in 24 h of the onset of symptoms. Plasma cytokines and interleukins will be collected at admission and 24 h after and will be measured using enzyme-linked immunosorbent assay (ELISA) to evaluate the difference in their variation among different gender, race and ethnicity and their association with various neurological outcomes. The primary exposures are biological sex (male, female) and race/ethnicity. Confounding variables include age, vascular risk factors, infarct size, stroke onset to presentation time, and identified stroke etiologies. Matched controls will be used for the comparison and evaluation of the difference among gender and race/ethnicities.CRISP is a prospective observational study that investigates the role and relationship of molecular biomarkers identifying specific and relevant targets pertinent for monitoring the progression and outcome in AS patients.Trial Registration: The study is registered on ClinicalTrial.gov: https://clinicaltrials.gov/ (NCT03297827).

Permissive microbiome characterizes human subjects with a neurovascular disease cavernous angioma.

Cavernous angiomas (CA) are common vascular anomalies causing brain hemorrhage. Based on mouse studies, roles of gram-negative bacteria and altered intestinal homeostasis have been implicated in CA pathogenesis, and pilot study had suggested potential microbiome differences between non-CA and CA individuals based on 16S rRNA gene sequencing. We here assess microbiome differences in a larger cohort of human subjects with and without CA, and among subjects with different clinical features, and conduct more definitive microbial analyses using metagenomic shotgun sequencing. Relative abundance of distinct bacterial species in CA patients is shown, consistent with postulated permissive microbiome driving CA lesion genesis via lipopolysaccharide signaling, in humans as in mice. Other microbiome differences are related to CA clinical behavior. Weighted combinations of microbiome signatures and plasma inflammatory biomarkers enhance associations with disease severity and hemorrhage. This is the first demonstration of a sensitive and specific diagnostic microbiome in a human neurovascular disease.